CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage

Science ◽  
2018 ◽  
Vol 360 (6384) ◽  
pp. 50-57 ◽  
Author(s):  
Hiroki Abe ◽  
Susumu Jitsuki ◽  
Waki Nakajima ◽  
Yumi Murata ◽  
Aoi Jitsuki-Takahashi ◽  
...  
Keyword(s):  
Brain Damage ◽  
Motor Function ◽  
Neural Plasticity ◽  
Internal Capsule ◽  
Cortical Reorganization ◽  
Dependent Manner ◽  
Small Compound ◽  
Function Recovery ◽  
Mediator Protein ◽  
Accelerate Rehabilitation

Brain damage such as stroke is a devastating neurological condition that may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic maleate, facilitated experience-driven synaptic glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid) receptor delivery and resulted in the acceleration of motor function recovery after motor cortex cryoinjury in mice in a training-dependent manner through cortical reorganization. Edonerpic bound to collapsin-response-mediator-protein 2 (CRMP2) and failed to augment recovery in CRMP2-deficient mice. Edonerpic maleate enhanced motor function recovery from internal capsule hemorrhage in nonhuman primates. Thus, edonerpic maleate, a neural plasticity enhancer, could be a clinically potent small compound with which to accelerate rehabilitation after brain damage.

scholarly journals Promotion of Poststroke Motor-Function Recovery with Repetitive Transcranial Magnetic Stimulation by Regulating the Interhemispheric Imbalance

2020 ◽  
Vol 10 (9) ◽  
pp. 648
Author(s):  
Xiaoxia Yuan ◽  
Yuan Yang ◽  
Na Cao ◽  
Changhao Jiang
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Motor Function ◽  
Neural Plasticity ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Noninvasive Brain Stimulation ◽  
Function Recovery ◽  
The Brain ◽  
Stimulation Technique ◽  
Positive Results

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain-stimulation technique that transiently modulates cerebral cortex excitability, achieving overall positive results in poststroke motor-function recovery. Excessive inhibition of the ipsilesional-affected hemisphere by the contralesional-unaffected hemisphere has seriously hindered poststroke motor-function recovery. Hence, intracortical disinhibition can be used as an approach to managing poststroke brain injury. This technique promotes neural plasticity for faster motor-function recovery. rTMS relieves unilateral inhibition of the brain function by regulatinga interhemispheric-imbalanced inhibition. This paper summarized 12 studies from 2016 to date, focusing on rTMS on motor function after acute and chronic stroke by regulating the interhemispheric imbalance of inhibitory inputs. Although rTMS studies have shown promising outcomes on recovery of motor functions in stroke patients, different intervention methods may lead to discrepancies in results. A uniform optimal stimulus model cannot routinely be used, mainly due to the stimulus schemes, stroke types and outcome-measuring differences among studies. Thus, the effect of rTMS on poststroke motor-function recovery should be investigated further to standardize the rTMS program for optimal poststroke motor-function recovery. More randomized, placebo-controlled clinical trials with standardized rTMS protocols are needed to ensure the effectiveness of the treatment.

Multimodal Neuroimaging Using Concurrent EEG/fNIRS for Poststroke Recovery Assessment: An Exploratory Study

2020 ◽  
Vol 34 (12) ◽  
pp. 1099-1110
Author(s):  
Rihui Li ◽  
Sheng Li ◽  
Jinsook Roh ◽  
Chushan Wang ◽  
Yingchun Zhang
Keyword(s):  
Motor Function ◽  
Premotor Cortex ◽  
Cortical Reorganization ◽  
Healthy Controls ◽  
Multimodal Neuroimaging ◽  
Stroke Patients ◽  
Functional Near Infrared Spectroscopy ◽  
Source Imaging ◽  
Eeg Source Imaging ◽  
Function Recovery

Background Persistent motor deficits are very common in poststroke survivors and often lead to disability. Current clinical measures for profiling motor impairment and assessing poststroke recovery are largely subjective and lack precision. Objective A multimodal neuroimaging approach was developed based on concurrent functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) to identify biomarkers associated with motor function recovery and document the poststroke cortical reorganization. Methods EEG and fNIRS data were simultaneously recorded from 9 healthy controls and 18 stroke patients during a hand-clenching task. A novel fNIRS-informed EEG source imaging approach was developed to estimate cortical activity and functional connectivity. Subsequently, graph theory analysis was performed to identify network features for monitoring and predicting motor function recovery during a 4-week intervention. Results The task-evoked strength at ipsilesional primary somatosensory cortex was significantly lower in stroke patients compared with healthy controls ( P < .001). In addition, across the 4-week rehabilitation intervention, the strength at ipsilesional premotor cortex (PMC) ( R = 0.895, P = .006) and the connectivity between bilateral primary motor cortices (M1) ( R = 0.9, P = .007) increased in parallel with the improvement of motor function. Furthermore, a higher baseline strength at ipsilesional PMC was associated with a better motor function recovery ( R = 0.768, P = .007), while a higher baseline connectivity between ipsilesional supplementary motor cortex (SMA)–M1 implied a worse motor function recovery ( R = −0.745, P = .009). Conclusion The proposed multimodal EEG/fNIRS technique demonstrates a preliminary potential for monitoring and predicting poststroke motor recovery. We expect such findings can be further validated in future study.

CRMP2 binding compound, T-817-maleic-acid, accelerates motor function recovery from brain damage

2017 ◽  
Vol 381 ◽  
pp. 595
Author(s):  
H. Abe ◽  
S. Jitsuki ◽  
W. Nakajima ◽  
Y. Murata ◽  
N. Higo ◽  
...  
Keyword(s):  
Brain Damage ◽  
Motor Function ◽  
Maleic Acid ◽  
Function Recovery

scholarly journals Maladaptive Plasticity for Motor Recovery after Stroke: Mechanisms and Approaches

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Naoyuki Takeuchi ◽  
Shin-Ichi Izumi
Keyword(s):  
Motor Function ◽  
Neural Plasticity ◽  
Motor Pattern ◽  
Movement Pattern ◽  
Competitive Interaction ◽  
Motor Recovery ◽  
Cortical Reorganization ◽  
Stroke Patients ◽  
Compensatory Movement ◽  
Maladaptive Plasticity

Many studies in human and animal models have shown that neural plasticity compensates for the loss of motor function after stroke. However, neural plasticity concerning compensatory movement, activated ipsilateral motor projections and competitive interaction after stroke contributes to maladaptive plasticity, which negatively affects motor recovery. Compensatory movement on the less-affected side helps to perform self-sustaining activity but also creates an inappropriate movement pattern and ultimately limits the normal motor pattern. The activated ipsilateral motor projections after stroke are unable to sufficiently support the disruption of the corticospinal motor projections and induce the abnormal movement linked to poor motor ability. The competitive interaction between both hemispheres induces abnormal interhemispheric inhibition that weakens motor function in stroke patients. Moreover, widespread disinhibition increases the risk of competitive interaction between the hand and the proximal arm, which results in an incomplete motor recovery. To minimize this maladaptive plasticity, rehabilitation programs should be selected according to the motor impairment of stroke patients. Noninvasive brain stimulation might also be useful for correcting maladaptive plasticity after stroke. Here, we review the underlying mechanisms of maladaptive plasticity after stroke and propose rehabilitation approaches for appropriate cortical reorganization.

Adaptive and Maladaptive Neural Plasticity Due to Facial Nerve Palsy

2016 ◽  
Vol 224 (2) ◽  
pp. 102-111 ◽  
Author(s):  
Carsten M. Klingner ◽  
Stefan Brodoehl ◽  
Gerd F. Volk ◽  
Orlando Guntinas-Lichius ◽  
Otto W. Witte
Keyword(s):  
Facial Nerve ◽  
Neural Plasticity ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Motor Nerve ◽  
Predictive Coding ◽  
Theoretical Framework ◽  
Cortical Reorganization ◽  
Nerve Lesion ◽  
Peripheral Facial Palsy

Abstract. This paper reviews adaptive and maladaptive mechanisms of cortical plasticity in patients suffering from peripheral facial palsy. As the peripheral facial nerve is a pure motor nerve, a facial nerve lesion is causing an exclusive deefferentation without deafferentation. We focus on the question of how the investigation of pure deefferentation adds to our current understanding of brain plasticity which derives from studies on learning and studies on brain lesions. The importance of efference and afference as drivers for cortical plasticity is discussed in addition to the crossmodal influence of different competitive sensory inputs. We make the attempt to integrate the experimental findings of the effects of pure deefferentation within the theoretical framework of cortical responses and predictive coding. We show that the available experimental data can be explained within this theoretical framework which also clarifies the necessity for maladaptive plasticity. Finally, we propose rehabilitation approaches for directing cortical reorganization in the appropriate direction and highlight some challenging questions that are yet unexplored in the field.

scholarly journals VI. A record of the results obtained, by electrical excitation of the so-called motor cortex and internal capsule in an orang-outang (Simia satyrus)

1890 ◽  
Vol 181 ◽  
pp. 129-158 ◽  
Keyword(s):  
Motor Cortex ◽  
Comparative Study ◽  
Motor Function ◽  
Trinity College ◽  
Internal Capsule ◽  
Electrical Excitation ◽  
Trinity College Dublin ◽  
Bonnet Monkey ◽  
Correct Estimate

Having been occupied with the study of the minute representation of motor function in the cortex of the Bonnet Monkey ( Macacus sinicus ), it seemed to us extremely necessary to investigate the character of such representation in the cortex of an anthropoid Ape, in order that we might form a more correct estimate of the mode of localisation in Man. A comparative study of the brains and habits of the more easily obtainable anthropoids showed clearly that for our object the Orang was more suitable than the Chimpanzee, in being likely to afford results nearer to those presumed to exist in Man. We therefore procured a young Orang which, in the opinion of Professor D. J. Cunningham, of Trinity College, Dublin, was about 21/2 years old. In addition to excitation of the cortex, we also investigated the movements obtained by stimulating the fibres of the internal capsule.

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